Age- and Temperature-Dependent Somatic Mutation Accumulation in Drosophila melanogaster

Using a transgenic mouse model harboring a mutation reporter gene that can be efficiently recovered from genomic DNA, we previously demonstrated that mutations accumulate in aging mice in a tissue-specific manner. Applying a recently developed, similar reporter-based assay in Drosophila melanogaster, we now show that the mutation frequency at the lacZ locus in somatic tissue of flies is about three times as high as in mouse tissues, with a much higher fraction of large genome rearrangements. Similar to mice, somatic mutations in the fly also accumulate as a function of age, but they do so much more quickly at higher temperature, a condition which in invertebrates is associated with decreased life span. Most mutations were found to accumulate in the thorax and less in abdomen, suggesting the highly oxidative flight muscles as a possible source of genotoxic stress. These results show that somatic mutation loads in short-lived flies are much more severe than in the much longer-lived mice, with the mutation rate in flies proportional to biological rather than chronological aging

Effect of Antihypertensive Therapy with Alpha Methyldopa on Levels of Angiogenic Factors in Pregnancies with Hypertensive Disorders

Antihypertensive drugs are believed to lower blood pressure in pre-eclampsia by direct or central vasodilatory mechanisms. However, they could also act by decreasing production of anti-angiogenic proteins involved in the pathophysiology of hypertension and proteinuria in pre-eclampsia (PE). The aim of our study was to evaluate the impact of antihypertensive therapy with alpha methyldopa on maternal circulating levels and placental production of soluble fms-like tyrosine kinase 1 (sFlt-1), soluble endoglin (sEng), vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) in hypertensive disorders of pregnancy

Missense mutation of Brain Derived Neurotrophic Factor (BDNF) alters neurocognitive performance in patients with mild traumatic brain injury: a longitudinal study

The predictability of neurocognitive outcomes in patients with traumatic brain injury is not straightforward. The extent and nature of recovery in patients with mild traumatic brain injury (mTBI) are usually heterogeneous and not substantially explained by the commonly known demographic and injury-related prognostic factors despite having sustained similar injuries or injury severity. Hence, this study evaluated the effects and association of the Brain Derived Neurotrophic Factor (BDNF) missense mutations in relation to neurocognitive performance among patients with mTBI. 48 patients with mTBI were prospectively recruited and MRI scans of the brain were performed within an average 10.1 (SD 4.2) hours post trauma with assessment of their neuropsychological performance post full Glasgow Coma Scale (GCS) recovery. Neurocognitive assessments were repeated again at 6 months follow-up. The paired t-test, Cohen’s d effect size and repeated measure ANOVA were performed to delineate statistically significant differences between the groups [wildtype G allele (Val homozygotes) vs. minor A allele (Met carriers)] and their neuropsychological performance across the time point (T1 = baseline/ admission vs. T2 = 6th month follow-up). Minor A allele carriers in this study generally performed more poorly on neuropsychological testing in comparison wildtype G allele group at both time points. Significant mean differences were observed among the wildtype group in the domains of memory (M = -11.44, SD = 10.0, p = .01, d = 1.22), executive function (M = -11.56, SD = 11.7, p = .02, d = 1.05) and overall performance (M = -6.89 SD = 5.3, p = .00, d = 1.39), while the minor A allele carriers showed significant mean differences in the domains of attention (M = -11.0, SD = 13.1, p = .00, d = .86) and overall cognitive performance (M = -5.25, SD = 8.1, p = .01, d = .66).The minor A allele carriers in comparison to the wildtype G allele group, showed considerably lower scores at admission and remained impaired in most domains across the timepoints, although delayed signs of recovery were noted to be significant in the domains attention and overall cognition. In conclusion, the current study has demonstrated the role of the BDNF rs6265 Val66Met polymorphism in influencing specific neurocognitive outcomes in patients with mTBI. Findings were more detrimentally profound among Met allele carriers

Thermal Perceptual Thresholds are typical in Autism Spectrum Disorder but Strongly Related to Intra-individual Response Variability

Individuals with autism spectrum disorder (ASD) are often reported to exhibit an apparent indifference to pain or temperature. Leading models suggest that this behavior is the result of elevated perceptual thresholds for thermal stimuli, but data to support these assertions are inconclusive. An alternative proposal suggests that the sensory features of ASD arise from increased intra-individual perceptual variability. In this study, we measured method-of-limits warm and cool detection thresholds in 142 individuals (83 with ASD, 59 with typical development [TD], aged 7–54 years), testing relationships with diagnostic group, demographics, and clinical measures. We also investigated the relationship between detection thresholds and a novel measure of intra-individual (trial-to-trial) threshold variability, a putative index of “perceptual noise.” This investigation found no differences in thermal detection thresholds between individuals with ASD and typical controls, despite large differences between groups in sensory reactivity questionnaires and modest group differences in intra-individual variability. Lower performance IQ, male sex, and higher intra-individual variability in threshold estimates were the most significant predictors of elevated detection thresholds. Although no psychophysical measure was significantly correlated with questionnaire measures of sensory hyporeactivity, large intra-individual variability may partially explain the elevated psychophysical thresholds seen in a subset of the ASD population

Effectiveness and tolerability of guselkumab in patients with psoriasis: A longitudinal Belgian retrospective multicenter study

No abstract availabl

Clinical Characteristics and Morbidity Associated With Coronavirus Disease 2019 in a Series of Patients in Metropolitan Detroit

Importance: In late December 2019, an outbreak caused by a novel severe acute respiratory syndrome coronavirus 2 emerged in Wuhan, China. Data on the clinical characteristics and outcomes of infected patients in urban communities in the US are limited. Objectives: To describe the clinical characteristics and outcomes of patients with coronavirus disease 2019 (COVID-19) and to perform a comparative analysis of hospitalized and ambulatory patient populations. Design, Setting, and Participants: This study is a case series of 463 consecutive patients with COVID-19 evaluated at Henry Ford Health System in metropolitan Detroit, Michigan, from March 9 to March 27, 2020. Data analysis was performed from March to April 2020. Exposure: Laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection. Main Outcomes and Measures: Demographic data, underlying comorbidities, clinical presentation, complications, treatment, and outcomes were collected. Results: Of 463 patients with COVID-19 (mean [SD] age, 57.5 [16.8] years), 259 (55.9%) were female, and 334 (72.1%) were African American. Most patients (435 [94.0%]) had at least 1 comorbidity, including hypertension (295 patients [63.7%]), chronic kidney disease (182 patients [39.3%]), and diabetes (178 patients [38.4%]). Common symptoms at presentation were cough (347 patients [74.9%]), fever (315 patients [68.0%]), and dyspnea (282 patients [60.9%]). Three hundred fifty-five patients (76.7%) were hospitalized; 141 (39.7%) required intensive care unit management and 114 (80.8%) of those patients required invasive mechanical ventilation. Male sex (odds ratio [OR], 2.0; 95% CI, 1.3-3.2; P = .001), severe obesity (OR, 2.0; 95% CI, 1.4-3.6; P = .02), and chronic kidney disease (OR, 2.0; 95% CI, 1.3-3.3; P = .006) were independently associated with intensive care unit admission. Patients admitted to the intensive care unit had longer length of stay and higher incidence of respiratory failure and acute respiratory distress syndrome requiring invasive mechanical ventilation, acute kidney injury requiring dialysis, shock, and mortality (57 patients [40.4%] vs 15 patients [7.0%]) compared with patients in the general practice unit. Twenty-nine (11.2%) of those discharged from the hospital were readmitted and, overall, 20.0% died within 30 days. Male sex (OR, 1.8; 95% CI, 1.1-3.1; P = .03) and age older than 60 years (OR, 5.3; 95% CI, 2.9-9.7; P \u3c .001) were significantly associated with mortality, whereas African American race was not (OR, 0.98; 95% CI, 0.54-1.8; P = .86). Conclusions and Relevance: In this review of urban metropolitan patients with COVID-19, most were African American with a high prevalence of comorbid conditions and high rates of hospitalization, intensive care unit admission, complications, and mortality due to COVID-19